DESCRIPTION: The overall objective of the research proposal is to determine th role of prenatal stress in the etiology of diabetes. The aim of this proposal is to examine the effect of chronic maternal immobilization stress of rats on glucose metabolism in the offspring. Specific Aim 1 is designed to identify th gestational period during which prenatal stress has maximal effect on birth weight and glucose metabolism of the offspring. Glucose metabolism will be evaluated by measuring basal fetal glucose and insulin levels and by the glucose tolerance test. Specific Aim 2 is designed to determine the ability of prenatally stressed rats to cope with chronic metabolic stress administered during adulthood by measuring their glucose metabolism after a chronic high fructose diet. The final studies are mechanistic in design, and will establish the role of maternal corticosterone in mediating the effects of prenatal stres on glucose metabolism in the offspring. Stress-induced increases in maternal corticosterone will be inhibited with cyanoketone and glucose metabolism will be examined in the offspring. Finally, the activity of placental 11b-hydroxysteroid dehydrogenase, which inactivates corticosterone, will be measured in chronically stressed pregnant rats to test the hypothesis that chronic prenatal stress decreases the placental level of this enzyme.